OpRegen®
for Dry AMD
On December 20, 2021, Lineage entered into an exclusive worldwide collaboration and license agreement with Roche and Genentech, a member of the Roche Group, for the development and commercialization of OpRegen for the treatment of ocular disorders, including advanced dry age-related macular degeneration (dry AMD) with geographic atrophy (GA) in a transaction worth up to $670 million in addition to double digit royalties. In January 2022, Lineage received a $50 million upfront payment from Genentech.
In November 2022, Genentech launched a Phase 2a, multicenter, open-label, single arm clinical study of RG6501 (OpRegen) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
In May 2024, we established a new services agreement with Genentech, a member of the Roche Group, to support ongoing development of OpRegen. Under this new agreement, Lineage will provide additional clinical, technical, training and manufacturing services that further support the ongoing advancement and optimization of the OpRegen program. These additional services will be fully funded by Genentech and include: (i) activities to support the ongoing Phase 1/2a study and currently-enrolling Phase 2a study; and (ii) additional technical training and materials related to Lineage’s cell therapy technology platform to support commercial manufacturing strategies.
Image adapted from scienceofamd.org
OpRegen is currently being evaluated in a Phase 2a study intended to optimize subretinal surgical delivery and evaluate safety and activity in up to 60 patients. The primary objectives of the study are to evaluate (i) the proportion of patients with subretinal surgical delivery of OpRegen to target regions under the retina, and (ii) to evaluate the safety of subretinal surgical delivery of OpRegen as measured by the incidence and severity of procedure-related adverse events at 3 months following surgery. A key secondary objective is to evaluate the proportion of patients with qualitative improvement in retinal structure, as determined by Optical Coherence Tomography (SD-OCT) imaging, within 3 months following surgery.
The FDA has granted OpRegen with Fast Track Designations and, as such, is on an expedited regulatory path that includes the ability for increased interfacing with the FDA during clinical development and enhanced favorability for marketing approval.
Clinical Data
In May 2024, 24 month visual acuity results from patients enrolled in the Phase 1/2a clinical study of OpRegen in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD), were presented at the 2024 Retinal Cell & Gene Therapy Innovation Summit.
- BCVA gains of +5.5 letters at 24 months in Cohort 4 patients (n=10)
- BCVA gains of +7.4 letters among Cohort 4 patients with extensive OpRegen bleb coverage of the GA lesion (n=5)
- Maintenance or increases in external limiting membrane (ELM) and retinal pigment epithelium (RPE) layers observed by optical coherence tomography (OCT) in patients with extensive bleb coverage of the GA lesion
- Data suggests OpRegen may counteract RPE cell dysfunction and cell loss in GA by providing support to remaining retinal cells, with effects observed through at least 2 years following a single administration
2024 Retinal Cell & Gene Therapy Innovation Summit Highlights:
- Improvement in visual acuity and outer retinal structure in patients with extensive OpRegen bleb coverage of their GA area was present at 12 months (primary endpoint) and persisted through 24 months
- BCVA gains in Cohort 4 patients (less advanced GA than in other cohorts) measured at 12 months were sustained at 24 months following a single subretinal administration of OpRegen
- Mean change in BCVA among treated eyes for patients (n=10) completing 2-year follow up was +5.5 letters (Early Treatment Diabetic Retinopathy Study [ETDRS] assessment)
- Effects were greater on average in the five (5) patients with extensive OpRegen coverage of atrophic areas at the time of surgical delivery
- In these patients’ treated eyes, the mean change in BCVA was +7.4 ETDRS letters for those completing 2-year follow-up (n=5)
- Maintenance or improvements in external limiting membrane (ELM) and RPE drusen complex (RPEDC) structure on OCT were observed in five patients in Cohort 4 with extensive OpRegen coverage of atrophic areas at the time of surgical delivery
- Mean improvement of RPEDC area compared with baseline was maintained in treated eyes from 12 months (+2.6 mm2; n=5) to 24 months (+2.6 mm2; n=4)
- In comparison, mean change in RPEDC area decreased in untreated fellow eyes from 12 months (-1.1 mm2; n=5) to 24 months (-2.8 mm2; n=4)
- Mean change in ELM area increased in treated eyes from 12 months (+0.4 mm2; n=5) to 24 months (+0.8 mm2; n=4)
- In comparison, mean change in ELM area decreased in untreated fellow eyes from 12 months (-1.3 mm2; n=5) to 24 months (-1.9 mm2; n=4)
- Overall, these data suggest that OpRegen RPE cells may counteract RPE cell dysfunction and loss in GA by providing support to the remaining retinal cells within atrophic areas and such effects are durable through at least 24 months after a single administration
The 2024 Retinal Cell & Gene Therapy Innovation Summit presentation is available on the Events and Presentations section of Lineage’s website.
BCVA gains in study eyes are sustained
in Cohort 4 (Less advanced GA) patients 24 Months Post-Treatment
Data cutoff: 30 Oct 2023. Image courtesy of David Telander, MD
Outer retinal structure analyzed using EyeNotate OCT segmentation algorithm
in Cohort 4 patients
Segmentation result generated by Genentech EyeNotate OCT segmentation algorithm, reviewed and corrected by a single masked expert grader.
BM, Bruch’s membrane; EZ, ellipsoid zone; i-, inner boundary of layer; ILM, internal limiting membrane; IPL, inner plexiform layer; o-, outer boundary of layer; OPL, outer plexiform layer; RNFL, retinal nerve fiber layer. Image courtesy of David Telander, MD
Maintenance or improvement of RPEDC was observed in patients with extensive OpRegen bleb coverage of GA
in Cohort 4 patients 24 Months Post-Treatment
RPEDC, retinal pigment epithelium drusen complex. Thick lines represent the mean and error bars represent standard error. Data cutoff: 30 Oct 2023. Image courtesy of David Telander, MD
Maintenance or improvement of ELM was observed in patients with extensive OpRegen bleb coverage of GA
in Cohort 4 patients 24 Months Post-Treatment
Thick lines represent the mean and error bars represent standard error. Data cutoff: 30 Oct 2023. Image courtesy of David Telander, MD
Greater BCVA gains with extensive OpRegen bleb coverage of GA
in Cohort 4 patients 24 Months Post-Treatment
Data cutoff: 30 Oct 2023. Image courtesy of David Telander, MD
Market Opportunity
AMD affects more than 30 million people worldwide and approximately 1.6 million people are newly diagnosed annually in the U.S.1 It is a leading cause of vision loss in people over the age of 60 in the developed world. There are two forms of AMD: “wet AMD,” which affects only 10-15% of patients and “dry AMD,” which affects 85-90% of patients.2
Sources: (1) Pennington and DeAngelis, Eye and Vision, 2016 3:34; (2) JM Seddon, Epidemiology of age-related macular degeneration. (AP Schachat, S Ryan eds.) Retina, 3rd ed. St. Louis, MO: Mosby; 2001;1039-50
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